The mouse surfeit locus contains a cluster of six genes associated with four CpG-rich islands in 32 kilobases of genomic DNA.
The clustered arrangement (no two adjacent genes are separated by more than 73 base pairs [bp] and two genes overlap by 133 bp at their 3' ends) of the four genes (Surf-1 to -4) identified so far in the mouse surfeit locus (T. Williams, J. Yon, C. Huxley, and M. Fried, Proc. Natl. Acad. Sci. USA 85:3527-3530, 1988) is the tightest gene clustering found in any mammalian genome to date and strongly suggests the possibility of cis-interaction and/or coregulation of gene expression. Thus, we are analyzing the surfeit genes in detail and are defining the extent of the cluster. Here we present the sequence of the entire Surf-4 gene and define the 3' and 5' extents of its mRNAs. The Surf-4 gene has heterogeneous transcriptional start sites, and its 5' end lies in a CpG-rich island. The gene specifies three mRNAs, with the two most abundant mRNAs differing in the locations of their 3' polyadenylation sites. Only the most abundant Surf-4 mRNA would overlap the 3' end of the Surf-2 gene by 133 bp. Two new genes (Surf-5 and Surf-6) have been identified in the surfeit gene cluster by Northern (RNA) blot analysis. The 5' end of Surf-6 lies within the CpG-rich island about 8 kilobases (kb) from the CpG-rich island containing the 5' end of Surf-3, and Surf-5 lies between Surf-3 and Surf-6. Thus, the cluster contains a unique arrangement of four CpG-rich islands within 32 kb associated with the 5' ends of the six surfeit genes. The neighboring CpG-rich islands have been located 500 and 100 kb distant on either side of the surfeit cluster, indicating that the end of the cluster of islands has been reached.
Huxley
C
C
Department of Eukaryotic Gene Organization and Expression, Imperial Cancer Research Fund, London, England.
Fried
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D015226:Dinucleoside Phosphates / Q000032:analysis*; D005784:Gene Amplification; D007939:Leukemia L1210 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014158:Transcription, Genetic
D004247:DNA; D015226:Dinucleoside Phosphates; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D015719:Single-Strand Specific DNA and RNA Endonucleases; C015772:CpG dinucleotide